CN111374965B - Water-soluble coenzyme Q10 inclusion compound with high stability and preparation method thereof - Google Patents
Water-soluble coenzyme Q10 inclusion compound with high stability and preparation method thereof Download PDFInfo
- Publication number
- CN111374965B CN111374965B CN201811622203.9A CN201811622203A CN111374965B CN 111374965 B CN111374965 B CN 111374965B CN 201811622203 A CN201811622203 A CN 201811622203A CN 111374965 B CN111374965 B CN 111374965B
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- China
- Prior art keywords
- water
- coenzyme
- soluble coenzyme
- inclusion compound
- soluble
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- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 title claims abstract description 211
- ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 title claims abstract description 210
- 235000017471 coenzyme Q10 Nutrition 0.000 title claims abstract description 210
- 229940110767 coenzyme Q10 Drugs 0.000 title claims abstract description 191
- 150000001875 compounds Chemical class 0.000 title claims abstract description 126
- 238000002360 preparation method Methods 0.000 title claims description 47
- 239000007864 aqueous solution Substances 0.000 claims abstract description 71
- 239000000463 material Substances 0.000 claims abstract description 59
- 229920002472 Starch Polymers 0.000 claims abstract description 48
- 239000008107 starch Substances 0.000 claims abstract description 48
- 235000019698 starch Nutrition 0.000 claims abstract description 48
- 239000003431 cross linking reagent Substances 0.000 claims abstract description 46
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 41
- 238000003756 stirring Methods 0.000 claims abstract description 24
- 238000001914 filtration Methods 0.000 claims abstract description 12
- 238000001035 drying Methods 0.000 claims abstract description 6
- 239000000243 solution Substances 0.000 claims abstract description 4
- 229940032147 starch Drugs 0.000 claims description 45
- 229920001661 Chitosan Polymers 0.000 claims description 25
- 229920000858 Cyclodextrin Polymers 0.000 claims description 19
- 238000010438 heat treatment Methods 0.000 claims description 18
- -1 sulfobutyl beta-cyclodextrin Chemical compound 0.000 claims description 15
- 239000003995 emulsifying agent Substances 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 13
- 238000010008 shearing Methods 0.000 claims description 11
- 239000001116 FEMA 4028 Substances 0.000 claims description 8
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims description 8
- 229960004853 betadex Drugs 0.000 claims description 8
- 235000011175 beta-cyclodextrine Nutrition 0.000 claims description 7
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 7
- 239000000194 fatty acid Substances 0.000 claims description 7
- 229930195729 fatty acid Natural products 0.000 claims description 7
- 238000000265 homogenisation Methods 0.000 claims description 7
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims description 6
- 239000011837 N,N-methylenebisacrylamide Substances 0.000 claims description 6
- ZIUHHBKFKCYYJD-UHFFFAOYSA-N n,n'-methylenebisacrylamide Chemical compound C=CC(=O)NCNC(=O)C=C ZIUHHBKFKCYYJD-UHFFFAOYSA-N 0.000 claims description 6
- 229920000856 Amylose Polymers 0.000 claims description 5
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 claims description 5
- 229940080345 gamma-cyclodextrin Drugs 0.000 claims description 5
- GUOCOOQWZHQBJI-UHFFFAOYSA-N 4-oct-7-enoxy-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)OCCCCCCC=C GUOCOOQWZHQBJI-UHFFFAOYSA-N 0.000 claims description 4
- 239000004135 Bone phosphate Substances 0.000 claims description 4
- 229920002774 Maltodextrin Polymers 0.000 claims description 4
- 239000005913 Maltodextrin Substances 0.000 claims description 4
- 150000001299 aldehydes Chemical class 0.000 claims description 4
- 229940035034 maltodextrin Drugs 0.000 claims description 4
- 239000001254 oxidized starch Substances 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 229940080313 sodium starch Drugs 0.000 claims description 4
- JPSKCQCQZUGWNM-UHFFFAOYSA-N 2,7-Oxepanedione Chemical compound O=C1CCCCC(=O)O1 JPSKCQCQZUGWNM-UHFFFAOYSA-N 0.000 claims description 3
- 229920000877 Melamine resin Polymers 0.000 claims description 3
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 claims description 3
- PCSMJKASWLYICJ-UHFFFAOYSA-N Succinic aldehyde Chemical compound O=CCCC=O PCSMJKASWLYICJ-UHFFFAOYSA-N 0.000 claims description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 150000008064 anhydrides Chemical class 0.000 claims description 3
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 claims description 3
- 239000004202 carbamide Substances 0.000 claims description 3
- WVJOGYWFVNTSAU-UHFFFAOYSA-N dimethylol ethylene urea Chemical compound OCN1CCN(CO)C1=O WVJOGYWFVNTSAU-UHFFFAOYSA-N 0.000 claims description 3
- IVJISJACKSSFGE-UHFFFAOYSA-N formaldehyde;1,3,5-triazine-2,4,6-triamine Chemical compound O=C.NC1=NC(N)=NC(N)=N1 IVJISJACKSSFGE-UHFFFAOYSA-N 0.000 claims description 3
- 235000013808 oxidized starch Nutrition 0.000 claims description 3
- 235000019832 sodium triphosphate Nutrition 0.000 claims description 3
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 claims description 3
- YZOUYRAONFXZSI-SBHWVFSVSA-N (1S,3R,5R,6R,8R,10R,11R,13R,15R,16R,18R,20R,21R,23R,25R,26R,28R,30R,31S,33R,35R,36R,37S,38R,39S,40R,41S,42R,43S,44R,45S,46R,47S,48R,49S)-5,10,15,20,25,30,35-heptakis(hydroxymethyl)-37,39,40,41,42,43,44,45,46,47,48,49-dodecamethoxy-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontane-36,38-diol Chemical compound O([C@@H]([C@H]([C@@H]1OC)OC)O[C@H]2[C@@H](O)[C@@H]([C@@H](O[C@@H]3[C@@H](CO)O[C@@H]([C@H]([C@@H]3O)OC)O[C@@H]3[C@@H](CO)O[C@@H]([C@H]([C@@H]3OC)OC)O[C@@H]3[C@@H](CO)O[C@@H]([C@H]([C@@H]3OC)OC)O[C@@H]3[C@@H](CO)O[C@@H]([C@H]([C@@H]3OC)OC)O3)O[C@@H]2CO)OC)[C@H](CO)[C@H]1O[C@@H]1[C@@H](OC)[C@H](OC)[C@H]3[C@@H](CO)O1 YZOUYRAONFXZSI-SBHWVFSVSA-N 0.000 claims description 2
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 claims description 2
- QGKBSGBYSPTPKJ-UZMKXNTCSA-N 2,6-di-o-methyl-β-cyclodextrin Chemical compound COC[C@H]([C@H]([C@@H]([C@H]1OC)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COC)[C@H]([C@@H]([C@H]3OC)O)O[C@H]3O[C@H](COC)[C@H]([C@@H]([C@H]3OC)O)O[C@H]3O[C@H](COC)[C@H]([C@@H]([C@H]3OC)O)O[C@H]3O[C@H](COC)[C@H]([C@@H]([C@H]3OC)O)O3)[C@H](O)[C@H]2OC)COC)O[C@@H]1O[C@H]1[C@H](O)[C@@H](OC)[C@@H]3O[C@@H]1COC QGKBSGBYSPTPKJ-UZMKXNTCSA-N 0.000 claims description 2
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 claims description 2
- CUJVBAPGYBSBHJ-YWBSARSQSA-N 2-[[(1R,3R,5R,6S,8R,10R,11S,13R,15R,16S,18R,20R,21R,23R,25R,26R,28R,30R,31R,33R,35R,36R,37R,38R,39R,40R,41R,42R,43R,44R,45R,46R,47R,48R,49R)-36,38,40,42-tetrakis(carboxymethoxy)-10,15-bis(carboxymethoxymethyl)-37,39,41,43,44,45,46,47,48,49-decahydroxy-20,25,30,35-tetrakis(hydroxymethyl)-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontan-5-yl]methoxy]acetic acid Chemical compound OC[C@H]1O[C@@H]2O[C@H]3[C@H](O)[C@@H](O)[C@H](O[C@@H]3COCC(O)=O)O[C@H]3[C@H](O)[C@@H](O)[C@H](O[C@@H]3COCC(O)=O)O[C@H]3[C@H](O)[C@@H](O)[C@H](O[C@@H]3COCC(O)=O)O[C@@H]3[C@@H](CO)O[C@H](O[C@@H]4[C@@H](CO)O[C@H](O[C@@H]5[C@@H](CO)O[C@H](O[C@H]1[C@H](OCC(O)=O)[C@H]2O)[C@H](O)[C@H]5OCC(O)=O)[C@H](O)[C@H]4OCC(O)=O)[C@H](O)[C@H]3OCC(O)=O CUJVBAPGYBSBHJ-YWBSARSQSA-N 0.000 claims description 2
- 229920001612 Hydroxyethyl starch Polymers 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- JVFGXECLSQXABC-UHFFFAOYSA-N ac1l3obq Chemical compound O1C(C(C2O)O)C(COCC(C)O)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC(C(O)C2O)C(COCC(O)C)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC2C(O)C(O)C1OC2COCC(C)O JVFGXECLSQXABC-UHFFFAOYSA-N 0.000 claims description 2
- AZSFNUJOCKMOGB-UHFFFAOYSA-K cyclotriphosphate(3-) Chemical compound [O-]P1(=O)OP([O-])(=O)OP([O-])(=O)O1 AZSFNUJOCKMOGB-UHFFFAOYSA-K 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 229940050526 hydroxyethylstarch Drugs 0.000 claims description 2
- 150000004693 imidazolium salts Chemical class 0.000 claims description 2
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 229920000223 polyglycerol Polymers 0.000 claims description 2
- 229940014800 succinic anhydride Drugs 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 4
- NSDYIDKTTPXCRH-UHFFFAOYSA-N 6-guanidinohexanoic acid Chemical compound NC(=N)NCCCCCC(O)=O NSDYIDKTTPXCRH-UHFFFAOYSA-N 0.000 claims 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 claims 1
- UNXRWKVEANCORM-UHFFFAOYSA-I triphosphate(5-) Chemical compound [O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O UNXRWKVEANCORM-UHFFFAOYSA-I 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 7
- 238000004132 cross linking Methods 0.000 abstract description 3
- 238000005538 encapsulation Methods 0.000 description 13
- 238000000605 extraction Methods 0.000 description 13
- 239000000126 substance Substances 0.000 description 11
- 238000005516 engineering process Methods 0.000 description 9
- 230000010355 oscillation Effects 0.000 description 8
- 238000004108 freeze drying Methods 0.000 description 6
- UGTZMIPZNRIWHX-UHFFFAOYSA-K sodium trimetaphosphate Chemical compound [Na+].[Na+].[Na+].[O-]P1(=O)OP([O-])(=O)OP([O-])(=O)O1 UGTZMIPZNRIWHX-UHFFFAOYSA-K 0.000 description 6
- 238000007599 discharging Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 238000001694 spray drying Methods 0.000 description 5
- 239000005515 coenzyme Substances 0.000 description 4
- 239000002537 cosmetic Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- UUGXJSBPSRROMU-UHFFFAOYSA-N 2,3-dimethoxy-5-methyl-2-<(all-E)-3',7',11',15',19',23',27',31',35'-nonamethylhexatriaconta-2',6',10',14',18',22',26',30',34',nonaenyl>cyclohexa-2,5-dien-1,4-dion Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O UUGXJSBPSRROMU-UHFFFAOYSA-N 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 2
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- 238000001514 detection method Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- QUBQYFYWUJJAAK-UHFFFAOYSA-N oxymethurea Chemical compound OCNC(=O)NCO QUBQYFYWUJJAAK-UHFFFAOYSA-N 0.000 description 2
- 229950005308 oxymethurea Drugs 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical group O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 238000012356 Product development Methods 0.000 description 1
- LWZFANDGMFTDAV-BURFUSLBSA-N [(2r)-2-[(2r,3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O LWZFANDGMFTDAV-BURFUSLBSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001278 adipic acid derivatives Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- VBICKXHEKHSIBG-UHFFFAOYSA-N beta-monoglyceryl stearate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000008811 mitochondrial respiratory chain Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000004537 pulping Methods 0.000 description 1
- NPCOQXAVBJJZBQ-UHFFFAOYSA-N reduced coenzyme Q9 Natural products COC1=C(O)C(C)=C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)C(O)=C1OC NPCOQXAVBJJZBQ-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- KYKFCSHPTAVNJD-UHFFFAOYSA-L sodium adipate Chemical compound [Na+].[Na+].[O-]C(=O)CCCCC([O-])=O KYKFCSHPTAVNJD-UHFFFAOYSA-L 0.000 description 1
- 239000001601 sodium adipate Substances 0.000 description 1
- 235000011049 sodium adipate Nutrition 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007962 solid dispersion Substances 0.000 description 1
- 235000011067 sorbitan monolaureate Nutrition 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000002298 terpene group Chemical group 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940035936 ubiquinone Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0204—Specific forms not provided for by any of groups A61K8/0208 - A61K8/14
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/35—Ketones, e.g. benzophenone
- A61K8/355—Quinones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/732—Starch; Amylose; Amylopectin; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/56—Compounds, absorbed onto or entrapped into a solid carrier, e.g. encapsulated perfumes, inclusion compounds, sustained release forms
Abstract
The invention provides a water-soluble coenzyme Q10 inclusion compound with high stability, wherein a water solution of the water-soluble coenzyme Q10 inclusion compound is heated to 10-90 ℃, then a cross-linking agent is added, stirring reaction is carried out for 1-20 hours, and after filtration, drying is carried out, thus obtaining the water-soluble coenzyme Q10 inclusion compound with high stability. In the water-soluble coenzyme Q10 inclusion compound aqueous solution, the inclusion wall material of the coenzyme Q10 is starch wall material, and the water content is 50-95% of the mass of the water-soluble coenzyme Q10 inclusion compound aqueous solution; the adding amount of the cross-linking agent is 0.0005-0.02% of the mass of the water-soluble coenzyme Q10 inclusion compound aqueous solution. According to the invention, the terminal group treatment mode of crosslinking between hydrophilic terminal groups-OH outside the starch wall material is promoted by the crosslinking agent containing the polyfunctional group, so that the inlet port of the starch wall material is effectively blocked, the use stability of the water-soluble coenzyme Q10 inclusion compound is greatly improved, and the application field of the water-soluble coenzyme Q10 inclusion compound is further expanded.
Description
Technical Field
The invention belongs to the field of chemistry, and relates to a water-soluble coenzyme Q10 inclusion compound with high stability and a preparation method thereof.
Background
Coenzyme Q10 (CoQ 10), also known as ubiquinone, is a lipophilic chemical substance that is endogenously synthesized in human and various animal and plant cells. It consists of 1 benzoquinone ring linked to 1 side chain containing 10 isoprenoid units. CoQ10 is an indispensable important physiological substance in human body, and its chemical structural characteristics determine that it has many important physiological functions in human body, it is an important transmission substance in vital activity, is a critical substance for mitochondrial respiratory chain rate-limiting reaction, and plays an important role in cell energy generation and biological activity enhancement. CoQ10 is an unobtainable compound integrating medical use, nutrition and health care, and has been increasingly valued and developed in the fields of medicine, cosmetics, foods, health care products and the like, and is also inevitably applied more and more widely.
However, coQ10 has some drawbacks in practical applications, such as: the bioavailability and stability of CoQ10 are effectively improved by adopting a preparation technology, which is a hot spot of research at present. In response to the situation that CoQ10 exists in application, various methods for improving the bioavailability of the CoQ10, such as solid dispersion technology, inclusion compound technology, emulsion technology and the like, have been developed in recent years, and the water solubility of coenzyme is improved through the preparation technology so as to improve the bioavailability of the coenzyme and meet the market demand. Among them, inclusion compound technology is a better technology for solving the problem of CoQ10 solubility, and thus is widely used.
Because the starch has a lipophilic cavity and a hydrophilic end group, the starch can be used as a good coating wall material of the coenzyme Q10 to prepare the water-soluble coenzyme Q10.CN200510048010.3 discloses a technology for preparing a water-soluble coenzyme Q10 composition by gamma-cyclodextrin and mannitol. Cn101053556.B discloses a technique for preparing hydroxypropyl beta-cyclodextrin inclusion compound of coenzyme Q10 by a grinding method or a stirring method. CN102698284.B discloses a method for preparing the same by coenzyme Q10/amylose inclusion compound. CN108719988A discloses a coenzyme Q10 inclusion compound and a preparation process thereof, and through the repulsion of a hydrophilic diluent, coQ10 can be better kept in a cyclodextrin cavity, the inclusion rate of the coenzyme Q10-cyclodextrin inclusion compound is improved, and the stability of CoQ10 in a solid state is further improved.
In the above technology, the inclusion treatment is carried out on CoQ10 by using starch inclusion wall materials, so that the solubility of CoQ10 is improved. Some patents also improve the inclusion rate of the inclusion compound by a certain means, but the above process method is only aimed at the problems of the inclusion process of the CoQ10, such as the inclusion amount, the encapsulation rate and the like, and does not further consider the instability problem of the inclusion compound of the CoQ10 in practical application. Because the starch inclusion wall material is adopted for inclusion, coQ10 enters the cavity of the starch wall material through a certain physical means, but the entry is not irreversible, and in the further application process of the CoQ10 inclusion compound, especially in the fields of medical treatment, cosmetics, food and beverage and the like, various surfactants, other fat-soluble substances and partial water-soluble substances can form competition relation with the CoQ10 and enter the cavity of the starch wall material, so that the CoQ10 is extruded out of the cavity, the stability of the CoQ10 inclusion compound is reduced, and the use and preservation effect of the product are greatly reduced, so that the CoQ10 inclusion compound is greatly limited in practical application.
Therefore, further development is needed to improve the stability of CoQ10 inclusion compounds in practical applications.
Disclosure of Invention
The first aim of the invention is to provide a preparation method of a water-soluble coenzyme Q10 inclusion compound with high stability, so as to improve the stability of the CoQ10 inclusion compound in practical application.
In order to achieve the above purpose, the present invention adopts the following technical scheme:
the preparation method of the water-soluble coenzyme Q10 inclusion compound with high stability comprises the steps of heating a water solution of the water-soluble coenzyme Q10 inclusion compound to 10-90 ℃, adding a cross-linking agent, stirring for reacting for 1-20 hours, filtering, and drying to obtain the water-soluble coenzyme Q10 inclusion compound with high stability, wherein:
in the water-soluble coenzyme Q10 inclusion compound aqueous solution, the inclusion wall material of the coenzyme Q10 is starch wall material, and the water content is 50-95% of the mass of the water-soluble coenzyme Q10 inclusion compound aqueous solution;
the adding amount of the cross-linking agent is 0.0005-0.02% of the mass of the water-soluble coenzyme Q10 inclusion compound aqueous solution;
the cross-linking agent is selected from: one or more of dibasic or tribasic compounds, aldehydes, amino or imino compounds, and anhydrides.
According to the invention, the water-soluble coenzyme Q10 inclusion compound aqueous solution can be prepared by pulping commercially available water-soluble coenzyme Q10 inclusion compound serving as a raw material with water, and then reacting the water-soluble coenzyme Q10 inclusion compound aqueous solution with a cross-linking agent to carry out end group treatment.
The water-soluble coenzyme Q10 inclusion compound aqueous solution can also be prepared from raw materials such as coenzyme Q10, starch wall materials, emulsifying agents and the like, and can be directly reacted with a cross-linking agent before drying to carry out end group treatment.
Preferably, in the above preparation method, the preparation of the water-soluble coenzyme Q10 clathrate aqueous solution comprises the following steps:
(1) Adding starch wall materials and emulsifying agents with the formula amount into water, heating to 50-80 ℃, adding coenzyme Q10 with the formula amount, and respectively carrying out high-speed shearing and high-pressure homogenization to obtain homogenized materials;
(2) And (3) adding the low molecular weight chitosan with the formula amount into the homogeneous material in the step (1), and stirring and dissolving to obtain the water-soluble coenzyme Q10 inclusion compound aqueous solution.
In the step (1), the mass ratio of the coenzyme Q10 to the starch wall material to the emulsifying agent to the low molecular weight chitosan is 1 (1.375-95): 0.05-0.5): 0.075-6; the water consumption is 2-20 times of the mass of the starch wall material.
According to the invention, in the step (1), the rotating speed of the high-speed shearing is 1000-10000 r/min, and the time is 5-50min; the pressure of the high-pressure homogenization is 100-2000 bar, and the high-pressure homogenization is circulated for 2-10 times.
According to the invention, the starch-based wall material is selected from one or more of amylose, maltodextrin, oxidized starch, hydroxyethyl starch, sodium starch octenyl succinate, carboxymethylated starch, beta-cyclodextrin and derivatives thereof, gamma-cyclodextrin and derivatives thereof.
According to the present invention, the beta-cyclodextrin derivative is selected from one or more of hydroxypropyl beta-cyclodextrin, sulfobutylbeta-cyclodextrin, methyl beta-cyclodextrin, 2, 6-dimethyl beta-cyclodextrin, carboxymethyl beta-cyclodextrin and hydroxybutylbeta-cyclodextrin. Those skilled in the art will readily appreciate that the above-described β -cyclodextrin derivatives can be applied as starch-based wall materials in the present invention to produce similar beneficial technical effects.
According to the invention, the gamma-cyclodextrin derivative is hydroxypropyl gamma-cyclodextrin.
According to the present invention, the emulsifier is selected from one or more of polyoxyethylene sorbitan fatty acid ester (i.e. tween), sorbitan fatty acid ester (i.e. span), sucrose fatty acid ester (i.e. SE for short), polyethylene glycol fatty acid ester, monoglyceride and polyglycerol ester.
According to the present invention, in the step (2), the molecular weight of the low molecular weight chitosan is 5000 to 10000.
According to the invention, the dibasic or tribasic compounds include tripolyphosphates, trimetaphosphate salts, citrate salts, polycarboxylic acid imidazolium salts, polycarboxylic acid guanidino derivatives and adipic acid salts; the aldehydes include glutaraldehyde, succinaldehyde and melamine formaldehyde; the acid anhydride includes succinic anhydride, adipic anhydride and phthalic anhydride; the amino or imino compound comprises urea, dimethylol ethylene urea and N, N-methylene bisacrylamide.
Preferably, the water-soluble coenzyme Q10 inclusion compound aqueous solution is heated to 30-70 ℃, then the cross-linking agent is added, and the mixture is stirred and reacted for 3-6 hours.
Preferably, in the water-soluble coenzyme Q10 inclusion compound aqueous solution, the water content is 65.0-94.9% of the mass of the water-soluble coenzyme Q10 inclusion compound aqueous solution;
the adding amount of the cross-linking agent is 0.00085-0.0162% of the mass of the water-soluble coenzyme Q10 inclusion compound aqueous solution.
Preferably, the adding amount of the cross-linking agent is 0.01-0.05% of the starch wall material amount in the water-soluble coenzyme Q10 inclusion compound; in the step (1), the water consumption is 5-10 times of the mass of the starch wall material.
According to the invention, the drying step after the reaction of adding the crosslinking agent adopts the drying mode of other coenzyme Q10 inclusion compounds in the prior art, such as low-pressure spray drying and freeze drying.
A second object of the present invention is to provide a highly stable water-soluble coenzyme Q10 clathrate produced by the above method.
Compared with the prior art, the invention has the following beneficial technical effects:
(1) According to the preparation method of the water-soluble coenzyme Q10 inclusion compound with high stability, disclosed by the invention, the inlet port of the starch wall material is effectively blocked by a terminal group treatment mode of crosslinking between hydrophilic terminal groups-OH outside the starch wall material by the crosslinking agent containing the polyfunctional group, so that the external steric hindrance of the starch wall material of the prepared water-soluble coenzyme Q10 inclusion compound is increased, and in the subsequent practical application process, surfactants, other fat-soluble substances and part of water-soluble substances are difficult to enter a starch cavity through steric hindrance, so that the coenzyme Q10 included in the starch cavity is effectively prevented from being extruded, the use stability of the water-soluble coenzyme Q10 inclusion compound is greatly improved, and the application field of the water-soluble coenzyme Q10 inclusion compound is further expanded.
(2) When the water-soluble coenzyme Q10 inclusion compound aqueous solution is prepared, low-molecular-weight chitosan is added, the end group of the starch wall material is subjected to end group crosslinking treatment under the action of the intermediate of the low-molecular-weight chitosan, and the end group is crosslinked and encapsulated in molecules and among molecules by taking the low-molecular-weight chitosan as a transmission intermediate, so that the end capping efficiency can be further improved.
Meanwhile, as the positive charge amino group of the low molecular weight chitosan is introduced into a new charge repulsive layer, the repulsive effect of the water-soluble coenzyme Q10 inclusion compound on other competitive components is further improved, and the stability of the water-soluble coenzyme Q10 inclusion compound is further improved.
(3) The water-soluble coenzyme Q10 inclusion compound with high stability has the characteristics of good stability and wide application range.
Detailed Description
The invention will be further illustrated with reference to specific examples. It should be understood that the following examples are illustrative of the present invention and are not intended to limit the scope of the present invention.
In the following examples:
the low molecular weight chitosan is a commercial product, and the molecular weight is 5000-10000.
Coenzyme Q10 is a commercially available product such as coenzyme Q10 from the trade company of the san francisco.
The water-soluble coenzyme Q10 inclusion compound aqueous solution can be prepared by raw materials such as starch, coenzyme Q10, water and the like; the water-soluble coenzyme Q10 inclusion compound aqueous solution can also be prepared by commercially available water-soluble coenzyme Q10 inclusion compound and water.
Commercially available water-soluble coenzyme Q10 inclusion compounds, for example:
commercial sample 1: water-soluble coenzyme Q10 inclusion compound purchased from biotechnology company of Shaanxi province.
Commercial sample 2: water-soluble coenzyme Q10 inclusion complexes purchased from certain cosmetic and health product development companies in the United states.
In the following examples, other materials are commercially available.
EXAMPLE 1 preparation of Water-soluble coenzyme Q10 clathrate
The preparation method of the water-soluble coenzyme Q10 inclusion compound comprises the following steps:
(1) Adding 95g of maltodextrin and 0.5g of Tween 80 into 475g of water, heating to 55 ℃, adding 1g of coenzyme Q10, shearing at a high speed for 15min under a condition of 3000r/min, homogenizing for 3 times in a high-pressure homogenizer at a high pressure of 600bar, and discharging to obtain a homogenized material.
(2) And (3) adding 6g of low molecular weight chitosan into the homogeneous material in the step (1), and stirring and dissolving to obtain the water-soluble coenzyme Q10 inclusion compound aqueous solution.
(3) Heating the water-soluble coenzyme Q10 inclusion compound aqueous solution in the step (2) to 35 ℃, adding 0.0475g of cross-linking agent N, N-methylene bisacrylamide, stirring and reacting for 3 hours, filtering, and performing low-pressure spray drying to obtain the water-soluble coenzyme Q10 inclusion compound with high stability.
Wherein, the adding amount of the cross-linking agent is 0.05 percent of the mass of the starch wall material-maltodextrin, and the adding amount of the cross-linking agent is 0.0082 percent of the water-soluble coenzyme Q10 inclusion compound aqueous solution. The mass ratio of the coenzyme Q10 to the starch wall material to the emulsifier to the low molecular weight chitosan is 1:95:0.5:6. In this example, the water content was 82.3% by mass of the aqueous solution of the water-soluble coenzyme Q10 clathrate.
EXAMPLE 2 preparation of Water-soluble coenzyme Q10 clathrate
The preparation method of the water-soluble coenzyme Q10 inclusion compound comprises the following steps:
(1) Adding 55g of oxidized starch and 2g of span 20 into 550g of water, heating to 70 ℃, adding 40g of coenzyme Q10, shearing at high speed for 25min under 7000r/min, homogenizing for 8 times in a high-pressure homogenizer at high pressure of 1200bar, and discharging to obtain a homogenized material.
(2) And (3) adding 3g of low molecular weight chitosan into the homogeneous material in the step (1), and stirring and dissolving to obtain the water-soluble coenzyme Q10 inclusion compound aqueous solution.
(3) Heating the water-soluble coenzyme Q10 inclusion compound aqueous solution in the step (2) to 55 ℃, adding 0.0055g of cross-linking agent glutaraldehyde, stirring and reacting for 6 hours, filtering, and freeze-drying to obtain the water-soluble coenzyme Q10 inclusion compound in the embodiment.
Wherein, the adding amount of the cross-linking agent is 0.01 percent of the mass of the starch wall material-oxidized starch. The addition amount of the cross-linking agent is 0.00085% of the water-soluble coenzyme Q10 inclusion compound aqueous solution. The mass ratio of the coenzyme Q10 to the starch wall material to the emulsifier to the low molecular weight chitosan is 1:1.375:0.05:0.075. In this example, the water content was 84.6% by mass of the aqueous solution of the water-soluble coenzyme Q10 clathrate.
EXAMPLE 3 preparation of Water-soluble coenzyme Q10 clathrate
The preparation method of the water-soluble coenzyme Q10 inclusion compound comprises the following steps:
(1) Adding 80g of beta-cyclodextrin and 1.0g of Tween 20 into 600g of water, heating to 60 ℃, adding 20g of coenzyme Q10, shearing at a high speed for 50min under the condition of 1000r/min, homogenizing for 5 times in a high-pressure homogenizer at a high pressure of 1000bar, and discharging to obtain a homogenized material.
(2) And (3) adding 4.5g of low molecular weight chitosan into the homogeneous material in the step (1), and stirring and dissolving to obtain the water-soluble coenzyme Q10 inclusion compound aqueous solution.
(2) Heating the water-soluble coenzyme Q10 inclusion compound aqueous solution in the step (1) to 45 ℃, adding 0.024g of cross-linking agent sodium trimetaphosphate, stirring for reacting for 5 hours, filtering, and performing low-pressure spray drying to obtain the water-soluble coenzyme Q10 inclusion compound in the embodiment.
Wherein the addition amount of the cross-linking agent is 0.03 percent of the mass of the starch wall material beta-cyclodextrin. The addition amount of the cross-linking agent is 0.0034 percent of the water-soluble coenzyme Q10 inclusion compound aqueous solution. The mass ratio of the coenzyme Q10 to the starch wall material to the emulsifier to the low molecular weight chitosan is 1:4:0.05:0.225. In this example, the water content was 85.0% by mass of the aqueous solution of the water-soluble coenzyme Q10 clathrate.
EXAMPLE 4 preparation of Water-soluble coenzyme Q10 clathrate
The preparation method of the water-soluble coenzyme Q10 inclusion compound comprises the following steps:
(1) 60g of sodium starch octenyl succinate and 1.5g of SE-15 are added into 400g of water, heated to 65 ℃, 10g of coenzyme Q10 is added, sheared for 20min at a high speed under the condition of 6500r/min, homogenized for 7 times in a high-pressure homogenizer at a high pressure of 800bar, and discharged to obtain a homogenized material.
(2) And (3) adding 5g of low molecular weight chitosan into the homogeneous material in the step (1), and stirring and dissolving to obtain the water-soluble coenzyme Q10 inclusion compound aqueous solution.
(3) Heating the water-soluble coenzyme Q10 inclusion compound aqueous solution in the step (2) to 30 ℃, adding 0.03g of cross-linking agent N, N-methylene bisacrylamide, stirring and reacting for 4 hours, filtering, and performing low-pressure spray drying to obtain the water-soluble coenzyme Q10 inclusion compound in the embodiment.
Wherein the adding amount of the cross-linking agent is 0.05 percent of the mass of the starch wall material-sodium starch octenyl succinate. The addition amount of the cross-linking agent is 0.0063% of the water-soluble coenzyme Q10 inclusion compound aqueous solution. The mass ratio of the coenzyme Q10 to the starch wall material to the emulsifier to the low molecular weight chitosan is 1:6:0.15:0.5. In this example, the water content was 83.9% by mass of the aqueous solution of the water-soluble coenzyme Q10 clathrate.
EXAMPLE 5 preparation of Water-soluble coenzyme Q10 clathrate
The preparation method of the water-soluble coenzyme Q10 inclusion compound comprises the following steps:
(1) Adding 72g of gamma-cyclodextrin and 1.5g of stearic acid monoglyceride into 500g of water, heating to 50 ℃, adding 30g of coenzyme Q10, shearing at a high speed for 15min under the condition of 6000r/min, homogenizing for 10 times in a high-pressure homogenizer at a high pressure of 100bar, and discharging to obtain a homogenized material.
(2) And (3) adding 4g of low molecular weight chitosan into the homogeneous material in the step (1), and stirring and dissolving to obtain the water-soluble coenzyme Q10 inclusion compound aqueous solution.
(3) Heating the water-soluble coenzyme Q10 inclusion compound aqueous solution in the step (2) to 60 ℃, adding 0.025g of crosslinking agent dimethylol urea, stirring and reacting for 6 hours, filtering, and freeze-drying to obtain the water-soluble coenzyme Q10 inclusion compound of the embodiment.
Wherein the addition amount of the cross-linking agent is 0.036% of the mass of the starch wall material-gamma-cyclodextrin. The addition amount of the cross-linking agent is 0.0041% of the water-soluble coenzyme Q10 inclusion compound aqueous solution. The mass ratio of the coenzyme Q10 to the starch wall material to the emulsifier to the low molecular weight chitosan is 1:2.4:0.05:0.14. In this example, the water content was 82.3% by mass of the aqueous solution of the water-soluble coenzyme Q10 clathrate.
EXAMPLE 6 preparation of Water-soluble coenzyme Q10 clathrate
The preparation method of the water-soluble coenzyme Q10 inclusion compound comprises the following steps:
(1) Adding 65g of beta-cyclodextrin and 2g of polyethylene glycol 400 monolaurate into 325g of water, heating to 65 ℃, adding 30g of coenzyme Q10, shearing at high speed for 5min under 10000r/min, homogenizing for 5 times at 1500bar high pressure in a high-pressure homogenizer, and discharging to obtain a homogenized material.
(2) And (3) adding 8g of low molecular weight chitosan into the homogeneous material in the step (1), and stirring and dissolving to obtain the water-soluble coenzyme Q10 inclusion compound aqueous solution.
(3) Heating the water-soluble coenzyme Q10 inclusion compound aqueous solution in the step (2) to 55 ℃, adding 0.01625g of cross-linking agent phthalic anhydride, stirring and reacting for 6 hours, filtering, and freeze-drying to obtain the water-soluble coenzyme Q10 inclusion compound in the embodiment.
Wherein the addition amount of the cross-linking agent is 0.025 percent of the mass of the starch wall material-beta-cyclodextrin. The addition amount of the cross-linking agent is 0.0038 percent of the water-soluble coenzyme Q10 inclusion compound aqueous solution. The mass ratio of the coenzyme Q10 to the starch wall material to the emulsifier to the low molecular weight chitosan is 1:2.17:0.067:0.27. In this example, the water content was 75.6% by mass of the aqueous solution of the water-soluble coenzyme Q10 clathrate.
EXAMPLE 7 preparation of Water-soluble coenzyme Q10 clathrate
The preparation method of the water-soluble coenzyme Q10 inclusion compound comprises the following steps:
(1) 50g of amylose and 0.8g of triglycerin oleate are added into 500g of water, heated to 50 ℃, 5g of coenzyme Q10 is added, high-speed shearing is carried out for 30min under the condition of 8000r/min, then homogenization is carried out for 2 times in a high-pressure homogenizer at 2000bar, and the material is discharged, thus obtaining a homogenized material.
(2) And (3) adding 10g of low molecular weight chitosan into the homogeneous material in the step (1), and stirring and dissolving to obtain the water-soluble coenzyme Q10 inclusion compound aqueous solution.
(3) Heating the water-soluble coenzyme Q10 inclusion compound aqueous solution in the step (2) to 45 ℃, adding 0.02g of cross-linking agent imidazole-4, 5-dicarboxylic acid sodium, stirring and reacting for 6 hours, filtering, and freeze-drying to obtain the water-soluble coenzyme Q10 inclusion compound in the embodiment.
Wherein the addition amount of the cross-linking agent is 0.04 percent of the mass of the starch wall material-amylose. The addition amount of the cross-linking agent is 0.0035 percent of the water-soluble coenzyme Q10 inclusion compound aqueous solution. The mass ratio of the coenzyme Q10 to the starch wall material to the emulsifier to the low molecular weight chitosan is 1:10:0.16:2. In this example, the water content was 88.4% by mass of the aqueous solution of the water-soluble coenzyme Q10 clathrate.
Example 8 preparation of Water-soluble coenzyme Q10 clathrate
The preparation method is the same as in example 2, except that in step (3), the aqueous solution of the water-soluble coenzyme Q10 clathrate is heated to 10℃and 0.015g succinic aldehyde is used instead of glutaraldehyde, and the reaction is stirred for 20 hours.
EXAMPLE 9 preparation of Water-soluble coenzyme Q10 clathrate
The preparation was the same as in example 2, except that 0.02g of melamine formaldehyde was used instead of glutaraldehyde.
Example 10 preparation of Water-soluble coenzyme Q10 clathrate
The preparation process was the same as in example 1, except that in the above step (1), the amount of water used was 190g. In the step (3), the water-soluble coenzyme Q10 inclusion compound aqueous solution is heated to 90 ℃, and 0.024g of urea is adopted to replace N, N-methylene bisacrylamide, and the reaction is stirred for 1h.
Wherein, the adding amount of the cross-linking agent is 0.0162 percent of the water-soluble coenzyme Q10 inclusion compound aqueous solution. In this example, the water content was 65.0% by mass of the aqueous solution of the water-soluble coenzyme Q10 clathrate.
EXAMPLE 11 preparation of Water-soluble coenzyme Q10 clathrate
The preparation was the same as in example 5 except that 0.0072g of dimethylol ethylene urea was used instead of dimethylol urea.
EXAMPLE 12 preparation of Water-soluble coenzyme Q10 clathrate
The preparation was the same as in example 1 except that in step (3), 0.03g of sodium tripolyphosphate was used instead of sodium trimetaphosphate.
EXAMPLE 13 preparation of Water-soluble coenzyme Q10 clathrate
The preparation was carried out in the same manner as in example 1 except that in step (3), 0.0095g of 6-guanidinoacetic acid hydrochloride was used instead of sodium trimetaphosphate.
EXAMPLE 14 preparation of Water-soluble coenzyme Q10 clathrate
The preparation process was the same as in example 1, except that in the above-mentioned step (1), the amount of water used was 1900g. In the step (3), the water-soluble coenzyme Q10 clathrate compound aqueous solution is heated to 90 ℃, and 0.019g of sodium citrate is adopted to replace sodium trimetaphosphate.
Wherein, the adding amount of the cross-linking agent is 0.0024 percent of the water-soluble coenzyme Q10 inclusion compound aqueous solution. In this example, the water content was 94.9% by mass of the aqueous solution of the water-soluble coenzyme Q10 clathrate.
EXAMPLE 15 preparation of Water-soluble coenzyme Q10 clathrate
The preparation was the same as in example 1, except that in step (3), 0.035g of sodium adipate was used instead of sodium trimetaphosphate.
EXAMPLE 16 preparation of Water-soluble coenzyme Q10 clathrate
The preparation was the same as in example 1, except that in step (3), 0.015g of adipic anhydride was used instead of sodium trimetaphosphate.
EXAMPLE 17 preparation of Water-soluble coenzyme Q10 clathrate
Commercial samples: 96.5g of water is added into 475g of water, and the mixture is stirred uniformly to prepare water-soluble coenzyme Q10 inclusion compound aqueous solution.
Heating the water-soluble coenzyme Q10 inclusion compound aqueous solution to 35 ℃, adding 0.0475g of cross-linking agent N, N-methylene bisacrylamide, stirring uniformly, continuing stirring for reaction for 3 hours, filtering, and performing low-pressure spray drying on the filtrate to obtain the water-soluble coenzyme Q10 inclusion compound of the embodiment.
Wherein, the adding amount of the cross-linking agent is 0.0083% of the mass of the water-soluble coenzyme Q10 inclusion compound aqueous solution. In this example, the water content was 83.1% by mass of the aqueous solution of the water-soluble coenzyme Q10 clathrate.
EXAMPLE 18 preparation of Water-soluble coenzyme Q10 clathrate
Commercial sample 2:97g, 550g of water is added, and the mixture is stirred uniformly to prepare the water-soluble coenzyme Q10 inclusion compound aqueous solution.
Heating the water-soluble coenzyme Q10 inclusion compound solution in the step (1) to 55 ℃, adding 0.0055g of cross-linking agent glutaraldehyde, stirring uniformly, continuing stirring for reaction for 6 hours, filtering, and freeze-drying to obtain the water-soluble coenzyme Q10 inclusion compound in the embodiment.
Wherein, the adding amount of the cross-linking agent is 0.00085 percent of the mass of the water-soluble coenzyme Q10 inclusion compound aqueous solution. In this example, the water content was 85.0% by mass of the aqueous solution of the water-soluble coenzyme Q10 clathrate.
EXAMPLE 19 evaluation of stability of Water-soluble coenzyme Q10 clathrate
And (3) taking a commercially available sample 1 and a commercially available sample 2, and carrying out stability detection on the water-soluble coenzyme Q10 inclusion compound prepared in examples 1-18, wherein the coenzyme content detection mode refers to the 2015 edition of Chinese pharmacopoeia.
Preparing a proper amount of water-soluble coenzyme Q10 inclusion compound into a water-soluble coenzyme Q10 inclusion compound aqueous solution with the concentration of 5wt%, adding 5ml of the water-soluble coenzyme Q10 inclusion compound aqueous solution into a 25ml colorimetric tube with a plug, adding 20ml of n-heptane, performing oscillation extraction, oscillating for 60 times per minute up and down, respectively sampling after oscillating for 0, 1, 2 and 5 minutes, detecting the amount of the extracted coenzyme Q10 in the sampling, and further evaluating the oscillation stability. Wherein, the encapsulation efficiency calculation formula is as follows:
encapsulation efficiency = [ (amount of coenzyme Q10 in clathrate-amount of extracted coenzyme Q10)/amount of coenzyme Q10 in clathrate ] ×100%.
The test results are shown in Table 1.
TABLE 1 encapsulation efficiency measurement results of Water-soluble coenzyme Q10 clathrate
As can be seen from table 1, under the same shaking extraction conditions, the encapsulation efficiency of the commercial sample 1 and the commercial sample 2 was reduced to 94.36 at the lowest level after shaking extraction for 1 minute, to 86.17 at the lowest level after shaking extraction for 2 minutes, and to 75.03 at the lowest level after shaking extraction for 5 minutes; the encapsulation efficiency reduction rate of 5 minutes of oscillation extraction reaches 23.68% and 24.97% respectively.
Examples 17 and 18 the end group treatment was carried out on commercial sample 1 and commercial sample 2, and the obtained water-soluble coenzyme Q10 inclusion compound had significantly improved encapsulation efficiency under the same conditions as those of commercial sample 1 and commercial sample 2, and the decrease rate of the encapsulation efficiency after shaking extraction for 5 minutes was 11.87% and 12.57%, respectively, which were half of those of commercial sample 1 and commercial sample 2.
Under the same oscillation extraction conditions, the water-soluble coenzyme Q10 inclusion compound prepared in the examples 1-16 still has an encapsulation rate of more than 99.29% after oscillation extraction for 1 min, still has an encapsulation rate of more than 98.75% after oscillation extraction for 2 min, and still has an encapsulation rate of more than 97.86% after oscillation extraction for 5 min. The average decrease in encapsulation efficiency of 5 minutes of shaking extraction was only 1.98%. Thus, the stability of the water-soluble coenzyme Q10 inclusion compound prepared in examples 1 to 16 is significantly improved compared with the commercially available sample 1 and the commercially available sample 2.
Therefore, under the same oscillation extraction time condition, the encapsulation efficiency of the water-soluble coenzyme Q10 prepared in the examples 1-18 is obviously higher than that of the commercial sample 1 and the commercial sample 2, and the stability of the water-soluble coenzyme Q10 inclusion compound prepared in the examples 1-18 is obviously higher than that of the commercial product, so that the water-soluble coenzyme Q10 inclusion compound can be ensured to effectively resist other components such as a surfactant, a surface active agent, other fat-soluble substances and partial water-soluble substances in the subsequent application process, especially in the fields of medical treatment, cosmetics, food and beverage and the like, the application requirements of the water-soluble coenzyme Q10 inclusion compound in different fields are greatly improved, and the application range of the coenzyme Q10 is effectively widened.
The above description of the specific embodiments of the present invention has been given by way of example only, and the present invention is not limited to the above described specific embodiments. Any equivalent modifications and substitutions for this practical use will also occur to those skilled in the art, and are within the scope of the present invention. Accordingly, equivalent changes and modifications are intended to be included within the scope of the present invention without departing from the spirit and scope thereof.
Claims (7)
1. A preparation method of a water-soluble coenzyme Q10 inclusion compound with high stability is characterized by heating a water solution of the water-soluble coenzyme Q10 inclusion compound to 10-90 ℃, then adding a cross-linking agent, stirring and reacting for 1-20 hours, filtering, and drying to obtain the water-soluble coenzyme Q10 inclusion compound with high stability, wherein:
in the water-soluble coenzyme Q10 inclusion compound aqueous solution, the inclusion wall material of the coenzyme Q10 is starch wall material, and the water content is 50-95% of the mass of the water-soluble coenzyme Q10 inclusion compound aqueous solution;
the adding amount of the cross-linking agent is 0.0005-0.02% of the mass of the water-soluble coenzyme Q10 inclusion compound aqueous solution;
the cross-linking agent is selected from: one or more of dibasic or tribasic compounds, aldehydes, amino or imino compounds, and anhydrides;
the preparation of the water-soluble coenzyme Q10 inclusion compound aqueous solution comprises the following steps:
(1) Adding starch wall materials and emulsifying agents with the formula amount into water, heating to 50-80 ℃, adding coenzyme Q10 with the formula amount, and respectively carrying out high-speed shearing and high-pressure homogenization to obtain homogenized materials; the high-speed shearing time is 5-50min;
(2) Adding low molecular weight chitosan with a formula amount into the homogeneous material in the step (1), and stirring and dissolving to obtain the water-soluble coenzyme Q10 inclusion compound aqueous solution;
in the step (2), the molecular weight of the low molecular weight chitosan is 5000-10000;
in the step (1), the mass ratio of the coenzyme Q10 to the starch wall material to the emulsifying agent to the low molecular weight chitosan is 1 (1.375-95): 0.05-0.5): 0.075-6; the water consumption is 2-20 times of the mass of the starch wall material;
the starch wall material is selected from one or more of amylose, maltodextrin, oxidized starch, hydroxyethyl starch, sodium starch octenyl succinate, carboxymethylated starch, beta-cyclodextrin and derivatives thereof, gamma-cyclodextrin and hydroxypropyl gamma-cyclodextrin;
the beta-cyclodextrin derivative is selected from one or more of hydroxypropyl beta-cyclodextrin, sulfobutyl beta-cyclodextrin, methyl beta-cyclodextrin, 2, 6-dimethyl beta-cyclodextrin, carboxymethyl beta-cyclodextrin and hydroxybutyl beta-cyclodextrin;
the dibasic or tribasic compound is selected from one or more of tripolyphosphate, trimetaphosphate, citrate, polycarboxylic acid imidazolium salt, 6-guanidinohexanoate and adipate; the aldehyde is selected from one or more of glutaraldehyde, succinaldehyde and melamine formaldehyde; the anhydride is selected from one or more of succinic anhydride, adipic anhydride and phthalic anhydride; the amino or imino compound is selected from one or more of urea, dimethylol ethylene urea and N, N-methylene bisacrylamide.
2. The method for producing a highly stable water-soluble coenzyme Q10 clathrate according to claim 1, wherein in the step (1), the rotation speed of the high-speed shearing is 1000 to 10000r/min; the pressure of the high-pressure homogenization is 100-2000 bar, and the high-pressure homogenization is circulated for 2-10 times.
3. The method for producing a highly stable water-soluble coenzyme Q10 clathrate according to claim 1, wherein the emulsifier is one or more selected from the group consisting of polyoxyethylene sorbitan fatty acid ester, sucrose fatty acid ester, polyethylene glycol fatty acid ester, monoglyceride and polyglycerol ester.
4. The method for producing a highly stable water-soluble coenzyme Q10 clathrate according to claim 1, wherein the aqueous solution of the water-soluble coenzyme Q10 clathrate is heated to 30 to 70℃and then a crosslinking agent is added thereto and stirred for 3 to 6 hours.
5. The method for producing a highly stable water-soluble coenzyme Q10 clathrate according to claim 1, wherein the water content in the water-soluble coenzyme Q10 clathrate aqueous solution is 65.0 to 94.9% by mass of the water-soluble coenzyme Q10 clathrate aqueous solution; the adding amount of the cross-linking agent is 0.00085-0.0162% of the mass of the water-soluble coenzyme Q10 inclusion compound aqueous solution.
6. The method for preparing the high-stability water-soluble coenzyme Q10 clathrate according to claim 1, wherein the adding amount of the crosslinking agent is 0.01-0.05% of the starch wall material amount in the water-soluble coenzyme Q10 clathrate; in the step (1), the water consumption is 5-10 times of the mass of the starch wall material.
7. The highly stable water-soluble coenzyme Q10 clathrate prepared according to any one of claims 1 to 6.
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